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Following investigation, FASEB Journal retracts paper after agreeing to run a correction

A contested retraction has punctuated the complicated saga of a 2003 paper in the FASEB Journal. (FASEB stands for the Federation of American Societies for Experimental Biology.)

A retraction notice for the paper, “Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure,” appeared in mid-June:

Regarding the article titled, “Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure,” by Susan Meier, Anja U. Brauer, Bernd Heimrich, Martin E. Schwab, Robert Nitsch, and Nicolai E. Savaskan, published in the June 2003 issue of The FASEB Journal (FASEB J., 2003 Jun;17(9):1153-1155; doi:10.1096/fj.02-0453fje). The editors of The FASEB Journal received a letter from Dr. Annette Gruters-Kieslich at Charite – Universitatsmedizin Berlin stating:

“In the year 2009 a series of reproaches in regard to scientiﬁc misconduct against Dr. Nicolai Savaskan reached the faculty of the Charite – Universitatsmedizin Berlin.”

“One of the manuscripts affected was published in the FASEB J in the year 2003: Meier S, Brauer AU, Heimrich B, Schwab ME, Nitsch R, Savaskan NE. FASEB J. 2003 Jun;17(9):1153–5. A well-recognized and top-class fact ﬁnding commission concluded that the publication contains gross ﬂaws. A key ﬁgure (Figure 14) and the conclusions drawn from it could not be underlined with the corresponding primary data. Therefore, the faculty has requested the senior author Dr. Nicolai Savaskan to retract the publication.”

In light of the “well-recognized and top-class fact ﬁnding” commission’s conclusions and the faculty’s recommendation to retract the article, the article has been retracted and all versions have been removed from the Web site.

came as a surprise and entirely contrary to expectations and preceding communication with the Editor-in-Chief Dr. Gerald Weissmann.

The authors had requested an erratum, not a retraction, and the journal had agreed to a correction.

I guess none of the coauthors of this paper do agree with the letter of Dr. Grüters-Kieslich. In contrary, all co-authors agreed on an erratum which was the result of the repetition of the original experiments done in the laboratory of Dr. R. Nitsch in Mainz, the co-senior author of the paper. Dr. Nitsch informed the appropriate university institutions about the data presentation error, repeated the experiments (using the same antibody from Dr. Schwab as 8 years ago!), and submitted an Erratum with experimental data from dedicated re-examinations of Fig. 14.

The data basically reproduce the findings, Savaskan said.

This erratum was considered by the appropriate institutions dealing with issues of good scientific practice at the Johannes Gutenberg-University Mainz, the Ombudsman and the president’s office. The result of the assessment of the issue by these institutions was communicated both to Dr. Nitsch and the German Science Foundation (DFG, the equivalent to the NIH), and the outcome was that there was no indication for any scientific misconduct of Dr. Nitsch, rather an honest error appeared in the original paper which could be cleared by a straight repetition of the original data. The editor-in-Chief eventually accepted our erratum, which was supported by consent from all authors, in March 29.

We tried asking the journal why it had reversed course. Weissmann referred us to FASEB’s Office of Publications, which responded:

The journal does not comment on the affairs of specific papers. The retraction is consistent with the journal’s policies, and the reason for retraction is stated in the retraction itself.

We also tried contacting Grüters-Kieslich for more details about the investigations, but she didn’t respond.

I should make the fact clear that the ‘top-class fact finding commission’ at the Charité as referred to by Dr. Grüters-Kieslich in her letter to the FASEB Journal (and cited in the retraction note) neither performed a proper hearing of myself nor contacted, informed or involved any of the co-authors working at other institutions. This latter fact totally ignores the regulations for good scientific practice and is against legal regulations.

This commission was in fact the second commission on this issue, and the first commission filed its report requiring an erratum on a data presentation error in figure 14 of our paper (which we regretfully have to admit). However, this error was not involving any original data (rather a wrong and evident miscalculation of a quantitative assessment of an actin blot, which, however, does not alter the underlying data at all), and this first commission formally stated that there was no proof of scientific misconduct.

The Charité, for reasons you might understand below, started a second commission, from which some members of had left during current proceedings for serious procedural lapses. This commission concluded that although original quantitative data for figure 14 exist and were found the archives, an error in the histogram in figure 14 was published that supports the suspicion of data manipulation and suggested that the paper should be therefore retracted.

A Charite press release about that second commission, which we translated roughly from German, said there was suspicion of data manipulation, but that it was not “court-proof evidence.” The release said that a third, independent commission would look for that evidence. Grüters-Kieslich, meanwhile, requested that the paper be retracted.

Savaskan disagrees with the move, and the authors want to see it reversed.

Still, we believe that all key findings of this paper are accurate and valid, and that the data presentation error in one out of 16 figures in total, as deplorable as it is, is no reason for retraction of data which are reproducible and have been published by independent labs.

28 thoughts on “Following investigation, FASEB Journal retracts paper after agreeing to run a correction”

Now here’s some real controversy! Why is FASEB’s Office of Publications stonewalling? Savaskan calls it a “… deplorable … data presentation error” but the data is nonetheless “reproducible.” The commission calls it “gross flaws” and says “a key figure and the conclusions drawn from it could not be underlined with the corresponding primary data.” So who is right? The commission, or someone, needs to explain this retraction better.

The March 2011 Bulfone-Paus retraction in the FASEB J was of work done at
The University Hospital Benjamin Franklin, Free University, Berlin,
part of the the same institution as the Savaskan August 2011 retraction.

Surely such things would have crossed the mind of the editor-in-chief of the FASEB Journal, Gerald Weissmann?

Is it plausible and to be presumed that the authors are foolish enough to make up data and place an easily identifiable error in a histogram (of the actin blot) that can otherwise easily be repeated and obtained through standard protocol and available antibodies, and which in itself has no impact on the final result?

There is a clear background behind this unjustified demand for retraction: obscure, confused and psychotic characterized emails sent to various scientists in Germany by Markus Kühbacher are used as a weapon by the Charité to continue aggression against the former Charité vice-dean Robert Nitsch, who was successful there for many years before being forced to leave on personal and political grounds instigated by the new CEO. This abuse of position and misuse of the Charité as a public institution of repute is well known throughout Germany.

Since none of the co-authors were involved by the commission, and the data has been readily replicated by the authors, why should the question of a retraction arise yet again at all? Although manipulation of the original data from eight years ago was insinuated, there was no proof acceptable in a court of law. Does this not invalidate any allegations to the contrary? Does our legal system not work on the premise “innocent until proven guilty”? Further prosecution when the initial evidence did not stand up in a court of law is comparable to the systems of trial to be found in autocratic countries devoid of an organised and fair legal system. Why would a second commission be requested, and even a third, solely in order to try and achieve the desired verdict—and that despite the lack of watertight evidence that would stand up in court of law?

The issue of scientific misconduct is indeed a serious offence. Besides being detrimental to the cause of science, it undermines the basic trust and faith fundamental to everything we undertake. As serious as misconduct and fraud are, unwarranted or false accusations and the flagrant misuse of position and the power of a renowned public institution constitute a comparable, if not even more serious breach of ethics and public trust. According to the in-depth investigation carried out by the Laborjournal, easily accessed and perused from the link on Dr. Ivanoransky’s blog, it is unequivocally concluded that there was no
fraud involved.

The Charité ought to revert to its fair and just standards, and not follow on blindly on the advice of someone who has left science due to his own incompetence and envy of the deserved success enjoyed by peers.

Dr. Ilker Eyupoglu is wrong and he knows that! His colleague Dr. Nicolai Savaskan has fabricated and falsified data – this is no longer in question after he lost three times in court. Even Dr. Robert Nitsch lost his court case against the Charité:

From the Pubmed record (go to Pubmed and enter “Savaskan” and “Eyupoglu” I believe that Ilker Eyupoglu ( post: August 14, 2011 at 4:31) might be somewhat conflicted. NE Savaskan and IY Eyupoglu have 11 publications together.

Should Ilker Eyupoglu not lay more emphasis on the facts of the matter, not on the purported motive of the person who pointed out what he thought was scientific misconduct? Even if the person who pointed out that he thought there was scientific misconduct did have a vendetta that would not alter the facts of the matter.

In science there is a reverse burden of proof in that the authors have to prove what they claimed (at the time of publication), not for others to show that it was not correct. It is up to the authors in this case to prove what they claimed with data from that publication, not for the person who pointed out what he thought was scientific misconduct to prove that there claims are false. Many of us could imagine what might likely be correct, publish it and just wait for others to “prove” it. If you made many claims some would probably turn out to be correct.

For viewers’ information The Times Higher Education World University Rankings places the Humboldt University, of which the Charite is part, at 71st in Europe, 9th in Germany.

@Clare Francis: I think you may be inconsistent on a couple of points.

1) You assert that @Ilker Eyopoglu should address facts rather than motives, but your main criticism is conflict of interest, i.e. a criticism of his motives or, minimally, his credibility.

2) Although you criticize @Ilker Eyopoglu for conflict of interest, you dismiss Markus Kühbacher’s asserted conflict of interest as irrelevant.

3) You correctly state that “in science … [the] burden of proof [is] that the authors have to prove what they claimed (at the time of publication), not for others to show that it was not correct.” But the issues here are (a) post-publication criticisms and (b) claims of fabrication. Clearly the burden has to be different in those cases. As to (a), a peer-reviewed publication is generally presumed to be correct (although the weight and nature of that presumption will vary). As to (b), no one presumes fabrication at any point — pre- or post-publication.

@Ilker Eyopoglu also raises a good due process question, which deserves more serious thought. How much process is due? I know the legal answer to that, at least in the US. Briefly, the minimum process is up to the institution, so long as the process is consistent and meets some very minimal standards of fairness. But, as he points out, the danger of too much process is unaddressed. In addition to the bureaucratization of science, one also has to worry about the politics and gamesmanship introduced by excessive use of quasi-legal thinking in science. Most important, process is expensive — or rather it has high costs. I refer not only to the waste of time and resources, or even the effects on the accused, but the effects of a lengthy inquiry — regardless of result — on people like @Ilker Eyopoglu, who are not accused of anything, have no involvement or voice in the particular issues at hand, no role in the process, but often stand to lose a great deal simply due to being near all the smoke and noise.

To confirm the obvious, yes, I’m a lawyer and have almost always represented defendants. So I have a bias, too.

My post was in response to Ilker Eyupoglu’s post. He (if it be the same person) does have 11 publications with NE Ssavaskan. He did not mention that fact.

I think that criticism of scientific papers as being in a civil court, not a criminal court (U.K.), in that you point out what you think is wrong with evidence, but it only depends on the “balance of probabilities”, not “beyond reasonable doubt”. You should examine the claims. Being versed in science should make the background of the accuser less important. Law courts still ask where you live, and do take less attention of people with “no fixed abode”. In science we should be able to look beyond that. The use of “court-proof evidence” (a phrase used by the institution in the main article above may encourage people think “beyond reasonable doubt”. They need to specifiy what kind of court.

Others (those who were not the reviewers, or editor) can only criticize the publication after it has been published, so I think that trying to make a new division of “post-publication criticisms” is irrelevant,obscures the issue, and it is not possible to have it otherwise. Allegations of fabrications is only a subdivision of “post-publication criticisms” and these take time. It takes times to gather the pieces of what you think is evidence. In fact they can happen at any future time. There are people who uncover things after centuries. We call them archeologists, and they get paid for it.

“Due process” is sometimes used as a defence of the indefencible. Most scientists, everyday, pick up,look at scientific papers and criticize them. They don’t need “due process” to do this. If you think that the paper is no good, or made up you say so. Many, not all, scientists, are willing to enter free discussion about scientific criticism of their work. That is the traditional method in the U.S. from my experience, and how things go forward “the elimination of the incorrect”. In this context “due process” starts to sound like political correctness. Science is either robust, or it is not. We are not talking about a particular assay or method here.

Your statement “peer-reviewed publication is generally presumed to be correct” is a Panglossian belief, which may not be correct. This blog is rapidly showing that peer review is not always correct, the percentage where it is correct is not known.

Undue affront caused by an accusation does remind me of the Max Planks rules:

“Ombudspersons should make it clear to staff that substantiated whistleblowing does
not constitute denunciation or behavior that is detrimental to their group; rather, it is
a necessary step in view of a suspected violation of scientific ethics. It is not the whistleblower
voicing a justified suspicion who damages colleagues or the institute concerned,
it is the scientist carrying out the misconduct.”

I agree that we should stick to the science and avoid legal thinking (either it is legal or it is not), (perhaps you used “quasi-legal” meaning that people do not understand what they think is legal?). A central part, perhaps the main part of science is open discourse, which is often lacking due to people needing to get grants and position. This should not be bound by legal etiquette, of the etiquette of the royal court. “Höflich” the German work for polite comes from the word der Hof = the royal court.

Talk about obfuscation! Let’s rather talk about the primary problem: does the error in the paper warrant a correction or a retraction? If the data is reproducible (possibly by other means) and the reproduction supports the primary conclusion of the paper, then a correction is warranted. If the data is wrong (regardless of why it is wrong, whether by innocent error or fabrication) and the corrected data does NOT support the conclusion, then a retraction must be made.
Which is it? No one appears to have addressed this point. I am (deliberately) writing from ignorance here because I think it should be straightforward to answer this question, either by the commission that examines the paper, or by interested bystanders.
There appears to be a lot of mudslinging going on here. I refer to the statement: “obscure, confused, and psychotic… emails” made by @Eyupoglu. “Psychotic” means “not in touch with reality” and that is rather a strong term to be throwing around here. @Francis points out a potential conflict of interest by @E… and leaves it to the reader to decide; I don’t think that is mudslinging, merely presentation of facts that might be of interest to a bystander. That fact might explain the use of terms such as “psychotic.”
We are not dealing with any court, whether civil or criminal, but a non-governmental (I hope) commission of inquiry set up by Charite; therefore I do not think the issue of “reasonable doubt” nor “preponderance of evidence” is relevant. We are rather dealing with “scientific certainty” and “reproducibility,” terms which do not have a defined meaning in court but are of great importance to scientists.
This is the kind of controversy for which I subscribed to Retraction Watch!

“Let’s rather talk about the primary problem: does the error in the paper warrant a correction or a retraction? If the data is reproducible (possibly by other means) and the reproduction supports the primary conclusion of the paper, then a correction is warranted.” (by conradseitz)

Accordingly, I am happy to provide the original data set (not just the erratum figure already accepted by the FASEB Journal) of the material which resulted form straight-forward repeating experiments done in my lab this spring using the SAME methodology (meaning: rats, performing the same lesion paradigm, the same antibody – stored for eight years in the refrigerator – and standard western blotting!). All this was standard and established methodology in the lab at the time of the initial experiments done over eight years ago! These data fully support the primary conclusion, in fact, they are entirely in line with what has been published in the paper!

Retraction watch Dr. Ivanoransky has obtained all these data, the only reason why this is not online here is a potential “double publication” of these data once the FASEB Journal will publish a correction (which I believe, will happen sooner or later, either by consent of the Charité, or upon a verdict by a German court on the illegal act requiring a retraction without contacting, hearing, or informing all coauthors).

Just send a request for the original data to me (robert.nitsch@unimedizin-mainz.de), and I will send the material for personal and confidential use to any interested scientist colleague, there is nothing to hide here. This will make this material publishable later as an erratum or corrigendum, but still open to critical outside assessment.

I appreciate the work of this blog a lot, making clear the major difference between honest error (which in fact occurred in our paper, and which the authors take responsibility for and deeply regret), and data manipulation or fabrication. I strongly believe that science without honest errors will never be possible, the only way to avoid this is not to publish anything at all!

I am confident that your new ‘original’ data fully support your old ‘original’ findings, otherwise you would not be willing to distribute them. Unfortunately, your ‘old’ original data did not. You explain this by an (honest) error.

Please strengthen the credibility of your case (credibility lies at the heart of science) and also answer the questions, Dr. Kühbacher posed on August 12:

Why do exist two EXCEL-files with the same date and time stamp with different “original data” for the same figure?

I agree strongly with Joerg Zwirner. Unless allegations of misconduct brought forth by Markus Kuehbacher and confirmed by the commission can be cleared with the old ‘original’ data, I agree with the commission that the right course of action is to retract the published article in question.

I for one, agree with Clare Francis. I do understand Toby White’s position regarding burden of proof in court of law, but in science, I do agree with Clare Francis that the burden of proof is up to the authors of manuscript.

Ilker Eyupoglu, I understand the frustration and anger that you may have toward Markus Kuehbacher, but sentences like:

…”obscure, confused and psychotic characterized emails sent to various scientists in Germany by Markus Kühbacher are used as a weapon by the Charité to continue aggression against the former Charité vice-dean Robert Nitsch, who was successful there for many years before being forced to leave on personal and political grounds instigated by the new CEO.”…

…”The Charité ought to revert to its fair and just standards, and not follow on blindly on the advice of someone who has left science due to his own incompetence and envy of the deserved success enjoyed by peers.”…

does not engender sympathy in me to your cause. Please stick to science if you wish to clear your name. I appreciate Robert Nitsch’s post, but like Clare Francis has stated, the burden of proof is on your shoulders, and you and Robert Nitsch have yet to counter the concern voiced by Markus Kuehbacher.

Even if your conclusions are upheld by Robert Nitsch’s experiments, misrepresenting or manipulating data is not a simple matter. I suspect that there were carelessness (or worse) involved in data collection and analysis, which is why Robert Nitsch had to repeat the experiments on his own. All of the original experimental hypothesis and accompanying conclusion may be validated, but if there were manipulations (or outright forgery) in the original data with intent to mislead or misrepresent, I don’t think one should be able to get away with claiming simple error, and that, Ilker Eyupoglu, is something you should seriously reflect upon, not name calling. Haven’t you realized by now that there have been people dismissed from academic positions purely because of poor record keeping?

Can someone explain who Markus Kühbacher is. Does he have some professional association with Drs Nitsch and/or Savaskan? Whats his motive for the alleged email campaign against Dr Nitsch? Do his allegations go beyond the FASB J paper?

In the Cell paper, fig. 2C P22 plots seem to be identical. However, I have no expertise in these experiments and this may well be a deliberate duplication for illustration purposes. Maybe somebody who has some understanding can enlighten me.

Any reason other than those papers being authored by Savaskan and Nitsch (among others) to ask about concerns? As far as I know, the manuscripts have not been mentioned in the debate at laborjournal.de or somewhere else.

Data published in both of these papers provides evidence that a protein called PRG1 is an enzyme with lipid phosphatase activity. Other workers have failed to reproduce this finding of PRG1 associated lipid phosphatase activity which, according to the authors, provides a mechanism for interesting effects associated with manipulations of PRG1 expression in neuronal cells. While there may be legitimate reasons for these discrepancies, in light of possible problems with other work from this group I simply wanted to find out if any of the data in these papers relating to the suggested function of PRG1 as a lipid phosphatase was being re-examined.

Karin Wiebauer has, in the Bulfone-Paus case, pointed out the use of “arrows of authority”, I believe in western blots, i.e. arrows pointing at things as if that meant anything in particular.
I am always unsure what arrows and arrowheads are supposed to to be pointing at. Something exactly at the tip, at something an arrowhead’s distance beyond the tip?

This is a general comment, using the publication referred to by “scotus August 16, 2011 at 1:23 pm” as the example. Cell. 2009 Sep 18;138(6):1222-35.

If you take a look at figure 1 you will notice arrows and arrowheads in many of the panels. It is common practice, but what do they signify? In some figure legends you are told, but in figure 1 D there is no clue in the legend. Are the arrows and arrowheads in each of the 3 uppers panels in figure1 D supposed to be pointing at things with the same properties? It is not obvious. In the right upper panel of figure 1D there are two arrowheads. One looks like it is pointing to a green cell (PRG-1), the other pointing to a red cell (ProSAP2). The arrows in the upper left and middle panels of figure are pointing at cells with nothing particularly in common when it comes to the colours they show. You could imagine many senarios to explain what you see. It is not obvious. I was always told to stick to what you can see in the images in the figures and not be taken in by the narrative.

This seems to be a controversial case. While a lot of the discussions rightly focus on the researchers involved , more attention should be given to the behaviour of the leadership of the institution (Charite) where the research in question has been carried out. If it is true that their investigation of the misconduct case was carried out without formally approaching and hearing ALL authors of the study before reaching the conclusion to write a retraction request to FASEB journal (as claimed by Savaskan), they have not followed proper procedure. Also, it is hard to understand why they need three (!) different commissions to go over this issue and still haven’t reached all conclusions. Researchers have to adhere to well defined standards of proper scientific conduct but the investigating institutions as well! It is notable that those accused are reacting to clarification requests from Retraction Watch but the Charite as well as FASEB journal are not.

Where are the EXCEL-files with the original data of the other 15 figures?

Therefore, I would kindly like to ask you to send me the original data of the unpublished erratum or corrigendum: “Just send a request for the original data to me (robert.nitsch@unimedizin-mainz.de), and I will send the material for personal and confidential use to any interested scientist colleague, there is nothing to hide here.”

I promise that the material will only be published if it contains, once again, false or falsified data.

Moreover, I will change my name into Roberto Kleinschmidt-Hendrix if it does not contain false or falsified data.

Best Regards,
Markus Kuehbacher

PS: Is Ilker Y. Eyupoglu right in his diagnosis of the relationships between members of your family and the CEO of the Charité?

The reproduciblity I mentioned was intended to mean, “reproducible by other researchers”, not by the same laboratory, as Dr Nitsch seems to have offered. It apears that, as scotus has stated, the work is not reproducible and thus questionable. If Marcus Kuehbacher’s assertion that he is not Roberto Kleinschmidt-Hendrix is not psychotic, then falsification is the answer to the questions raised and retraction is the appropriate response. Yes?

Whether image manipulations ultimately leads to retraction seems to be a matter of how well people are connected – see the rather “historic“ (2002/2007) case of a Baltimore paper in Science that showed very clearly that someone had manipulated and duplicated Western blot photos, but still wasn’t retracted. Have a look at Figure 3B, 15min and 60 min pulse. If you take the first 7 lanes, play a little bit with brightness and contrast you see that they are identical. Apparently someone found this, and Hoffmann and colleagues simply post a correction. It appears that one Baltimore scandal was enough for science. It is very interesting to read the correction…

It has been brought to our attention that, in Figure 2C of the article above, the in vivo recordings for P22 PRG-1 KO mice are identical. Upon re-examination of the original recordings, we found that the recording from the right hemisphere was mistakenly used to also represent the recording from the left hemisphere. All in vivo recordings and related figures were made by Sebastian Schuchmann.

The corrected figure with the appropriate recording for the left hemisphere is now presented below. This error was exclusive to P22 of Figure 2C and does not affect the article beyond Figure 2C, neither the original data underlying Figure 2C nor the description in the Results section or the conclusions resulting from these data. We apologize for the mistake and for any inconvenience caused to the readers, and we thank the alert reader who discovered the error.

The erratum of the publication in Cell entitled “Synaptic PRG-1 Modulates Excitatory Transmission via Lipid Phosphate-Mediated Signaling” is a real erratum in contrast to the mentioned but never published erratum in FASEB above. Comparing Figure 2C with Abbildung 27 on page 71 in the PhD thesis published already on May 13, 2009 (http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000010030?lang=en) shows that only the photograph of the mouse in Figure 2B might be still incorrect and should have been corrected too.

However, there are other questions:

Why are the SPW peak-triggered averages so similar in Figure 3C?

Did the authors pooled the samples for protein analysis of the PSD fractions prepared from PRG-1 KO and WT mice (Figure 6B) in contrast to the analysis presented in the PhD thesis in Abbildung 33 on page 77 with n (WT) = 8 and n (KO) = 8?

While I am sure that these questions can be answered, the questions related to the retracted publication about the NOGO protein and the not yet published erratum should not be answered without first speaking to an attorney.